This study is designed to assess the IgG subclass distribution and clonal diversity of the antibody response of children to two polysaccharide antigens, group A streptococcal carbohyrate (GAC) and phospholholin (PC). Studies in mice have demonstrated that the antibody response to certain polysaccharides is highly restricted to a particular IgG subclass, IgG3. Limited data from human adults suggest that IgG subclass restriction also characterizes the human antibody response to polysaccharide antigens. Further, serum concentrations of this subclass (IgG2) do not approach adult values until late in childhood. We postulate that a major factor in the failure of children to respond to polysaccharide antigens is restriction of antipolysaccharide antibodies to an immunoglobulin subclass which appears late in ontogeny. If this is true, we expect to verify subclass restriction of human anti-polysaccharide antibodies in all age groups and to find a correlation between the ability to respond to polysaride antigens and increasing total IgG2 concentrations in serum. In addition, we plan to test whether or not antibodies of the IgG2 subclass possess unique functional characteristics which provide protection from infections caused by encapsulated bacterial organisms. In order to accomplish this, we will study several groups of children with recurrent or unusually severe bacterial infections and search for abnormalities in the subclass distribution of their antibody response to bacterial polysaccharide antigens. Finally, a human hybridoma system will be developed to assess the functional capacity of monoclonal antibodies of various subclasses.